Arthritis involves both cartilage breakdown and new bone formation, and in many cases, leads to the loss of joint function. While there are some insights as to the mediators contributing to cartilage remodeling, there is only limited knowledge of the underlying molecular mechanisms of arthritis. At a cellular level, the articular chondrocyte plays a key role in both to cartilage breakdown and new bone growth, and this is likely to be reflected in changes in cellular transcriptional activity. The application of genomic approaches to the understanding of the complexities of arthritis promises to yield significant advances in the diagnosis and treatment of this prevalent disease of joint degeneration.
An important priority for the investigation and clinical application of potential therapies for arthritis is the identification of biochemical markers that could be used to assess various aspects of disease activity (Chevalier, X. (1997) Rev.Rhum. Engl. Ed. 64: 562-577.
Lohmander, L. S. (1997) Baillieres Clin. Rhematol. 11: 711-726). Current research in this field is focusing on a number of possible surrogate markers of arthritis that reflect metabolic changes in the joint associated with cartilage destruction and remodeling, including hyaluronate, cartilage oligomeric matrix protein, keratan sulfate, metalloproteinase activity, and various cytokines.
To identify gene products involved in human arthritis, the present inventors have analyzed the differences in mRNA populations in diseased cartilage compared to age-matched healthy cartilage using differential display RT-PCR (Hu, S-I, Carozza, M., Klein, M., Nantermet, P., Luk, D., and Crowl, R. M. (1998) J. Biol. Chem. 273: 34406-34412). The inventors have discovered a large protein, termed “adlican,” the presence of which in cartilage is strongly associated with arthritis, particularly osteoarthritis. An anti-peptide antibody was generated against the carboxy terminal sequence and used for immunoblot analysis to detect adlican protein in synovial fluid samples obtained from patients with arthritis.